(SLA-049) Post-approval Real-world Studies of RNA therapies in the EU: What Can We Learn from Study Characteristics?

Background: According to the American Society of Gene and Cell Therapy, as of Q3 2024, 34 RNA therapies had been approved globally (Gene, Cell, + RNA Therapy Landscape Report, American Society of Gene & Cell Therapy and Citeline, Q3 2024). Of these, 10 were approved in the EU (RNA vaccines excluded from this abstract). The landscape of RNA therapies is developing quickly, and it is important to understand how best to design post-approval real-world studies of these therapies.

Objectives: To provide an overview of key design characteristics of studies that are registered in the HMA-EMA Catalogue of RWD studies on RNA therapies approved in the EU (https://catalogues.ema.europa.eu/catalogue-rwd-studies , Accessed 29 January 2025).

Methods: Of the 10 (non-vaccine) RNA therapies approved in the EU, 9 had study entries in the HMA-EMA Catalogue of RWD studies, of which one had 3 studies. We extracted study design characteristics from each of these 11 studies.

Results: Of the 11 studies identified, study start date for seven (64%) was during 2020 or 2021 and was during Nov 2023 - Jan 2025 for the remaining. Median planned study duration (calculated from reported actual/planned start date until planned final study report date) was 9.6 years, with range of 1 - 11.3 years. Five studies included EU/EEA countries and/or UK only, and 6 included countries beyond EU/EEA and UK. Only one study was not required by any regulatory agency.
Five studies planned to assess safety only. Six studies planned to assess both safety and effectiveness, of which 1 also planned to assess natural history, and another also planned to assess drug utilization. The study entries rarely specified the planned duration of safety follow-up per patient. Three studies were pregnancy safety studies. The indications were rare diseases for 6 of the 10 RNA therapies.
Three studies indicated a comparator cohort. Data source was difficult to discern from the information provided in the structured data source field: Seven studies reported prospective patient-based data collection, 1 study named a secondary existing data source, and data source type was unclear for the other three. Median target size was 200 patients, with range of 10 - 500. Excluding the 3 pregnancy studies, and 1 study missing age: the planned study ages (number of studies) were: 18+ years (3), 12+ years (1), and all ages from birth (3).

Conclusions: Currently, it appears that real-world studies of RNA therapies approved in the EU are mostly conducted as part of regulatory requirements, with a focus on safety, and usually based on primary data collection.